Abstract

Abstract 1219

Poster Board I-241

Background

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been evaluated in several trials and has shown feasibility as first-line treatment of primary central nervous system lymphoma (PCNSL). However, the best conditioning regimen is still to be identified and high-dose chemotherapy of busulfan, cyclophosphamide, and etoposide (BuCyE) has not been tried although the regimen was shown to be effective for leukemia and systemic non-Hodgkin's lymphoma.

Methods

Between May 2005 and November 2008, 12 consecutive patients of PCNSL with pathologic diagnosis of diffuse large-B cell lymphoma were treated with the intent of upfront ASCT at Asan Medical Center, Seoul, Korea. We retrospectively analyzed the results of these patients. The treatment included induction chemotherapy of high-dose methotrexate/cytarabine (Abrey et al., JCO 21:4151, 2003), followed by BuCyE chemotherapy consisting of iv busulfan (3.2mg/kg from day -7 to day -5), iv cyclophosphamide (50mg/kg from day -3 to day -2), and etoposide (200mg/m2 every 12 hours from day -5 to day -4), and ASCT. Whole brain radiotherapy (WBRT) was reserved for patients who failed to achieve complete response (CR) after ASCT.

Results

Median age was 50 years (range, 33-65) and 9 were male. The test of cerebrospinal fluid (CSF) cytology came out to be positive for 3 patients. Eight patients achieved CR and 4 gained partial response (PR) after induction chemotherapy. All 12 patients managed to complete ASCT. Following ASCT, additional 2 patients gained CR, resulting in total number of 10 patients (83.3%). Patients who failed to reach CR were further treated with WBRT and 2 more patients achieved CR. Median duration of first CR was 12.8 months (95% confidence interval [CI], 4.6-20.9) at a median follow-up of 23.8 months (range, 8.8-50.7). Relapse of disease occurred in 7 patients (58.3%) and 5 of them were given salvage treatment (Table 1). Two patients could regain CR and sustained remission for more than 2 years. Two patients had died of disease at the time of analysis. Median event-free survival (EFS) from the first day of induction chemotherapy was 15.0 months (95% CI, 8.3-21.8) and median overall survival (OS) was not reached. The 2-year OS probability was 78.8% and 2-year EFS was 25.7%. No patient experienced veno-occlusive disease or treatment-related mortality (TRM). Three patients among those who were treated with WBRT or intrathecal chemotherapy developed leukoencephalopathy.

Conclusion

BuCyE chemotherapy might be an option of conditioning regimen for ASCT considering high CR rate of 83.3% and favorable toxicity profile in the treatment of PCNSL. However, high relapse rate of 58.3% suggests that more optimization of induction and conditioning chemotherapy is still required.

Table 1.

Patient data

Sex/Age Extent of disease Pre-ASCT Post-ASCT Brain RT (Gy) Overall Resp. 1st CR Duration (Mo) Relapse site Salvage Treatment Response to salvage Tx EFS (Mo) OS (Mo) Status Neuro-toxicity 
M/65 Brain PR PR 48 CR 41.6 50.7 50.7 AWoD Leg weakness 
F/55 Brain CR CR 451) CR 13.2 Brain & eye Chemotherapy2) PR 15.0 48.2 AWD LEP 
M/53 Brain CR CR CR 33.1 34.8 34.8 AWoD ND 
F/52 Brain PR CR CR 1.6 Brain WBRT CR 6.8 34.7 AWoD ND 
M/33 Brain & CSF CR CR CR 4.1 CSF IT-chemo CR 6.0 31.2 AWoD LEP 
M/43 Brain CR CR CR 8.1 Brain WBRT NE 9.7 25.0 Alive3) ND 
M/62 Brain CR CR CR 12.8 Brain WBRT PR 18.9 22.7 AWD ND 
M/63 Brain & CSF CR CR CR 6.2 Brain none 7.8 9.9 DOD ND 
M/48 Brain, CSF & maxillary sinus PR PR 44 CR 4.0 Brain none 13.0 13.2 DOD LEP 
F/47 Brain PR CR CR 6.4 12.9 12.9 AWoD ND 
M/45 Brain CR CR CR 6.4 9.5 9.5 AWoD ND 
M/48 Brain CR CR CR 6.3 8.8 8.8 AWoD ND 
Sex/Age Extent of disease Pre-ASCT Post-ASCT Brain RT (Gy) Overall Resp. 1st CR Duration (Mo) Relapse site Salvage Treatment Response to salvage Tx EFS (Mo) OS (Mo) Status Neuro-toxicity 
M/65 Brain PR PR 48 CR 41.6 50.7 50.7 AWoD Leg weakness 
F/55 Brain CR CR 451) CR 13.2 Brain & eye Chemotherapy2) PR 15.0 48.2 AWD LEP 
M/53 Brain CR CR CR 33.1 34.8 34.8 AWoD ND 
F/52 Brain PR CR CR 1.6 Brain WBRT CR 6.8 34.7 AWoD ND 
M/33 Brain & CSF CR CR CR 4.1 CSF IT-chemo CR 6.0 31.2 AWoD LEP 
M/43 Brain CR CR CR 8.1 Brain WBRT NE 9.7 25.0 Alive3) ND 
M/62 Brain CR CR CR 12.8 Brain WBRT PR 18.9 22.7 AWD ND 
M/63 Brain & CSF CR CR CR 6.2 Brain none 7.8 9.9 DOD ND 
M/48 Brain, CSF & maxillary sinus PR PR 44 CR 4.0 Brain none 13.0 13.2 DOD LEP 
F/47 Brain PR CR CR 6.4 12.9 12.9 AWoD ND 
M/45 Brain CR CR CR 6.4 9.5 9.5 AWoD ND 
M/48 Brain CR CR CR 6.3 8.8 8.8 AWoD ND 

Abbreviations: AWoD, alive without disease; AWD, alive with disease; DOD, dead of disease; IT-chemo, intrathecal chemotherapy composed of hydrocortisone, methotrexate, and cytarabine; LEP, leukoencephalopathy; ND, not definite; NE, not evaluated

1)

The patient was given WBRT after ASCT as she was assessed as PR at that time. However, the residual non-enhancing lesion by MRI did not change during follow-up and showed no hypermetabolism on PET. The lesion was concluded as post-biopsy change later.

2)

Chemotherapy of high-dose methotrexate/cytarabine and intravitreal methotrexate injection was done.

3)

The patient was lost to follow-up after WBRT but he is presumed to be alive according to the data of National Health Insurance Corporation.

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.